rs2287371

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000484549.6(CEP41):n.-5A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.423 in 1,611,662 control chromosomes in the GnomAD database, including 148,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12784 hom., cov: 33)

Exomes 𝑓: 0.43 ( 135254 hom. )

Consequence

CEP41
ENST00000484549.6 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.891

Publications

20 publications found

Variant links:

Genes affected

CEP41 (HGNC:12370): (centrosomal protein 41) This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

CEP41 Gene-Disease associations (from GenCC):

Joubert syndrome 15
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 7-130440971-T-G is Benign according to our data. Variant chr7-130440971-T-G is described in ClinVar as Benign. ClinVar VariationId is 261053.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP41	NM_018718.3 link	c.-5A>C		5_prime_UTR_variant	Exon 1 of 11	ENST00000223208.10	NP_061188.1	Q9BYV8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10 link	c.-5A>C		5_prime_UTR_variant	Exon 1 of 11	1	NM_018718.3	ENSP00000223208.4		Q9BYV8-1

Frequencies

GnomAD3 genomes

AF:

0.401

AC:

60889

AN:

151990

Hom.:

12758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.309

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.379

Gnomad NFE

AF:

0.402

Gnomad OTH

AF:

0.435

GnomAD2 exomes

AF:

0.458

AC:

114309

AN:

249758

AF XY:

0.458

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.658

Gnomad FIN exome

AF:

0.373

Gnomad NFE exome

AF:

0.402

Gnomad OTH exome

AF:

0.418

GnomAD4 exome

AF:

0.425

AC:

620347

AN:

1459554

Hom.:

135254

Cov.:

AF XY:

0.428

AC XY:

310923

AN XY:

726204

show subpopulations

African (AFR)

AF:

0.303

AC:

10137

AN:

33470

American (AMR)

AF:

0.567

AC:

25357

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

12027

AN:

26128

East Asian (EAS)

AF:

0.666

AC:

26427

AN:

39694

South Asian (SAS)

AF:

0.547

AC:

47214

AN:

86242

European-Finnish (FIN)

AF:

0.378

AC:

19603

AN:

51872

Middle Eastern (MID)

AF:

0.382

AC:

2203

AN:

5764

European-Non Finnish (NFE)

AF:

0.406

AC:

450959

AN:

1111310

Other (OTH)

AF:

0.438

AC:

26420

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

20669

41337

62006

82674

103343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14264

28528

42792

57056

71320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.401

AC:

60964

AN:

152108

Hom.:

12784

Cov.:

AF XY:

0.405

AC XY:

30127

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.310

AC:

12859

AN:

41502

American (AMR)

AF:

0.504

AC:

7706

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1604

AN:

3468

East Asian (EAS)

AF:

0.661

AC:

3408

AN:

5152

South Asian (SAS)

AF:

0.560

AC:

2698

AN:

4816

European-Finnish (FIN)

AF:

0.372

AC:

3937

AN:

10586

Middle Eastern (MID)

AF:

0.394

AC:

115

AN:

292

European-Non Finnish (NFE)

AF:

0.402

AC:

27297

AN:

67976

Other (OTH)

AF:

0.440

AC:

930

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1920

3840

5760

7680

9600

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.409

Hom.:

47326

Bravo

AF:

0.408

Asia WGS

AF:

0.652

AC:

2262

AN:

3478

EpiCase

AF:

0.406

EpiControl

AF:

0.400

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joubert syndrome 15

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.89

PromoterAI

0.13

Neutral

(source)

Mutation Taster

=147/153

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over